Vivien Measday, Ph.D.
My current research is the study of chromosome segregation in the budding yeast Saccharomyces cerevisiae (S. cerevisiae) using molecular biology and genomic tools. I am interested in understanding how chromosomes attach to spindle microtubules and segregate equally in mitosis. Spindle microtubules attach to the kinetochore which is composed of centromere DNA and associated proteins. There are over 40 kinetochore proteins identified in budding yeast that are grouped into inner, central and outer kinetochore categories. I am specifically interested in understanding the function of the outer kinetochore complexes and how they are regulated.
Most yeast researchers are currently studying basic cell processes using only a few strains of yeast. I will be expanding my research program to study chromosome biology in wine yeast. Interestingly, there are fundamental differences between laboratory yeast and industrial wine yeast. For example, wine yeast are able to grow in very high concentrations of sugar and ethanol which would kill a laboratory strain of yeast. Wine yeast also contain abnormal numbers of chromsomes (aneuploidy) whereas laboratory yeast have equal numbers of chromosomes. I will combine my molecular biology and genomics knowledge from laboratory S. cerevisiae to identify genes important for survival in an industrial growth environment and to study chromosome segregation in wine yeast. Studying aneuploid wine yeast will provide important insight into diseases hallmarked by abnormal chromosome numbers such as Down’s syndrome and cancer.
My lab is currently funded by the CIHR (Canadian Institutes of Health Research) and the MSFHR (Michael Smith Foundation for Health Research). I am funded to work on the role of the budding yeast kinetochore in mediating proper chromosome transmission and checkpoint response. I am specifically interested in the highly conserved Ndc80 complex which is required for attachment of microtubules to chromosomes. The Ndc80 complex is also involved in signaling the checkpoint response that prevents chromosomes from separating if they have not properly attached to the spindle.
There are approximately 4,700 nonessential genes in the budding yeast genome that have been systematically deleted by the yeast community. A method termed Synthetic Genetic Array (SGA) analysis, which was pioneered at the University of Toronto , has been developed which enables yeast researchers to perform genetic screens using the yeast deletion array. I n collaboration with Dr. Brenda Andrews and Dr. Charlie Boone at the University of Toronto, and Drs Kristin Baetz and Phil Hieter at the University of British Columbia, we have performed genome-wide SGA screens to identify yeast mutants that are defective in kinetochore function. We now have an exciting list of genes that have a role in chromosome segregation and we have the biological tools necessary to decipher their role in this process.
The media conditions that most yeast researchers use to study S. cerevisiae in the laboratory are not the physiologically relevant conditions that S. cerevisiae would find itself in nature. For example, in the lab we consider rich media to contain 2% glucose, whereas yeast found on a grape berry could be exposed to 20% sugars. Many of the genes in yeast have no known function because they have been deleted and the phenotype studied under limited condition. Many of these genes may have essential functions if tested for growth under different conditions. We have begun to address this by plating the yeast deletion set onto high sugar plates and analyzing which mutants are unable to grow. This work is being done in collaboration with Dr. Liz Conibear at the University of British Columbia who’s lab contains a specialized robot designed for pinning the yeast deletion set.
- Ma L., Ho K., Piggott N., Luo Z., Measday V. (2012) “Interactions between the kinetochore complex and the protein kinase A pathway in Saccharomyces cerevisiae” G3 (Bethesda). Jul 2(7):831-41
- Anderson, M. J., Barker, S. L., Boone, C. and Measday, V. (2011) “Identification of RCN1 and RSA3 as ethanol tolerant genes in Saccharomyces cerevisiae using a high copy barcoded library” FEMS Yeast Research Nov 12 (epub ahead of print, IF = 2.5)
- Fang, N. N., Ng, A. H. M., Measday, V. and Mayor, T. (2011) “Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turn-over of cytosolic misfolded proteins” Nature Cell Biology Oct 9; 13(11): 1344-52 (IF = 19.6)
- Piggott, N., Cook, M., Tyers, M. and Measday, V. (2011) “Genome-wide fitness profiles reveal a requirement for autophagy during yeast fermentation” G3: Genes, Genomes, Genetics 1: 353-367 (journal cover image from our paper, new journal, no IF yet)
- Walkey, C.J., Luo, Z., Borcher, C.H., Measday, V. and van Vuuren, H.J. (2011) “The Saccharomyces cerevisiae fermentation stress response protein Igd1/Yfr017p regulates glycogen levels by inhibiting the glycogen debranching enzyme” FEMS Yeast Research 11(6): 499-508 (IF = 2.5)
- Ma, L., McQueen, J., Cuschieri, L., Vogel, J. and Measday, V. (2007) “Spc24 and Stu2 promote spindle integrity when DNA replication is stalled” Molecular Biology of the Cell 18(8): 2805-2816 (IF = 6.0)
- Baetz, K., Measday, V. and Andrews, B. (2006) “Revealing Hidden Relationships Among Yeast Genes Involved in Chromosome Segregation Using Systematic Synthetic Lethal and Synthetic Dosage Lethal Screens” Cell Cycle Vol. 5, Issue 6: 592-595 (IF = 4.5)
- Monpetit, B., Thorne, K., Barrett, I., Andrews, K., Jadusingh, R., Hieter, P. and Measday, V. (2005) “Genome-wide synthetic lethal screens identify an interaction between the nuclear envelope protein, Apq12p, and the kinetochore in Saccharomyces cerevisiae” Genetics 171: 1-13. (IF = 4.3)
- Measday, V#., Baetz, K#., Guzzo, J., Yuen, K., Kwok, T., Sheikh, B., Ding, H., Ueta, R., Hoac, T., Cheng, B., Pot, I., Tong, A., Yamaguchi-Iwai, Y., Boone, C. Hieter, P. and Andrews, B. (2005) “Systematic yeast synthetic lethal and synthetic dosage lethality screens identify genes required for chromosome segregation” Proceedings of the National Academy of Sciences USA 102(39): 13956-13961. #authors contributed equally (IF = 10.6)
- Measday, V. and Hieter, P. (2004) “Kinetochore substructure comes to MIND” Nature Cell Biology 6(2): 94-95. (IF = 19.6)
- Pot, I., Measday, V., Snydsman, B., Cagney, G., Fields, S., Davis, T.N., Muller, E.G.D. and Hieter, P. (2003) “Chl4p and Iml3p are two new members of the budding yeast outer kinetochore” Molecular Biology of the Cell 14(2): 460-476. (IF = 6.0)
- Measday, V., Hailey, D.W., Pot, I., Givan, S., Hyland, K.M. Cagney, G., Fields, S., Davis, T.N. and Hieter, P. (2002) “Ctf3p, the Mis6 budding yeast homologue, interacts with Mcm22p and Mcm16p at the yeast outer kinetochore” Genes & Development 16(1): 101-113. (IF = 13.9)
- Measday, V. and Hieter, P. (2002) “Synthetic Dosage Lethality” Guide to Yeast Genetics and Molecular and Cell Biology, Parts B and C. Methods in Enzymology 350: 316-326. (IF = 2.2)
- McBride, H.J., Sil, A., Measday, V., Yu, Y., Moffat, J., Maxon, M.E., Herskowitz, I., Andrews, B. and Stillman, D. (2001) “The protein kinase Pho85 is required for asymmetric accumulation of the Ash1 protein in Saccharomyces cerevisiae” Molecular Microbiology 42(2): 345-353. (IF = 5.2)
- Macpherson, N., Measday, V., Moore L. and Andrews, B. (2000) “A yeast taf17 mutant requires the Swi6 transcriptional activator for viability and shows defects in cell cycle-regulated transcription” Genetics 154(4): 1561-1576. (IF=4.3)
- Measday, V., McBride, H., Moffat J., Stillman D. and Andrews, B. (2000) “Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast” Molecular Microbiology 35(4): 825-834. (IF = 5.2)
- Andrews, B. and Measday, V. (1998) “The cyclin family of budding yeast: abundant use of a good idea. Trends in Genetics” 14(2): 66-72. (IF = 9.3)
- Measday, V., Moore, L., Retnakaran, R., Lee, J., Donoviel, M., Neiman A. M. and Andrews, B. (1997) “A Family of Cyclin-Like Proteins that Interact with the Pho85 Cyclin-Dependent Kinase” Molecular and Cellular Biology 17(3): 1212-1223. (IF = 6.4)
- Ellis, C., Measday, V. and Moran, M.F. (1995) “Phosphorylation-dependent complexes of p120 Ras-specific GTPase-activating protein with p62 and p190” Methods in Enzymology 255: 179-192. (IF = 2.2)
- Measday, V., Moore, L., Ogas, J., Tyers, M. and Andrews, B. (1994) “The Pcl2 (OrfD)-Pho85 Cyclin-Dependent Kinase Complex, a Cell Cycle Regulator in Yeast” Science 266: 1391-1395. (IF = 31.8)